PharmPK Discussion - Calculation of F from blood versus urine data

On 29 Aug 2002 at 23:58:30, pkhalili (pkhalili.at.ualberta.ca) sent the message

Dear readers,We have been studying PK of a compound, which seems to exhibit dose-dependencyin its PK behaviour at higher doses. The F estimates that were obtained(basedon a linear kinetics assumption) and were calculated from the dose-correctedcomparisons of iv and oral data, were in the range of 0.68 to 1, depending onthe dose that was studied. The cumulative amount of the drug excretedunchanged in the urine (24 h collection)as fraction of the dose, however, wasvery small (~2-3%)in general. So, if we were to calculate F based on urinarydata, we would have very little bioavailability!Can anyone offer any explanation for this discrepancy?Is it possible that urinary excretion of this compound, had been alreadysaturated at doses lower than our lowest studied dose?

On 30 Aug 2002 at 00:09:48, pkhalili (pkhalili.-a-.ualberta.ca) sent the message

Dear readers,We have been studying PK of a compound, which seems to exhibit dose-dependencyin its PK behaviour at higher doses. The F estimates that were obtained(basedon a linear kinetics assumption) and were calculated from the dose-correctedcomparisons of iv and oral data, were in the range of 0.68 to 1, depending onthe dose that was studied. The cumulative amount of the drug excretedunchanged in the urine (24 h collection)as fraction of the dose, however, wasvery small (~2-3%)in general. So, if we were to calculate F based on urinarydata, we would have very little bioavailability!Can anyone offer any explanation for this discrepancy?Is it possible that urinary excretion of this compound, had been alreadysaturated at doses lower than our lowest studied dose?

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